CA3144324A1 - Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen - Google Patents
Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen Download PDFInfo
- Publication number
- CA3144324A1 CA3144324A1 CA3144324A CA3144324A CA3144324A1 CA 3144324 A1 CA3144324 A1 CA 3144324A1 CA 3144324 A CA3144324 A CA 3144324A CA 3144324 A CA3144324 A CA 3144324A CA 3144324 A1 CA3144324 A1 CA 3144324A1
- Authority
- CA
- Canada
- Prior art keywords
- dose
- treatment
- subject
- administered
- inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 title claims abstract description 381
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 title claims abstract description 381
- 238000002648 combination therapy Methods 0.000 title claims description 30
- 230000008685 targeting Effects 0.000 title description 11
- 238000011282 treatment Methods 0.000 claims abstract description 385
- 238000009739 binding Methods 0.000 claims abstract description 383
- 230000027455 binding Effects 0.000 claims abstract description 382
- 238000000034 method Methods 0.000 claims abstract description 246
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 79
- 201000011510 cancer Diseases 0.000 claims abstract description 57
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 44
- 239000000203 mixture Substances 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims description 110
- 210000004027 cell Anatomy 0.000 claims description 96
- 230000037452 priming Effects 0.000 claims description 81
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 72
- 229920001184 polypeptide Polymers 0.000 claims description 69
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 69
- 238000002560 therapeutic procedure Methods 0.000 claims description 63
- 229940124597 therapeutic agent Drugs 0.000 claims description 61
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 55
- 230000000694 effects Effects 0.000 claims description 50
- 229940079593 drug Drugs 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 44
- 238000001802 infusion Methods 0.000 claims description 44
- 150000001413 amino acids Chemical group 0.000 claims description 38
- 239000003795 chemical substances by application Substances 0.000 claims description 38
- 208000034578 Multiple myelomas Diseases 0.000 claims description 35
- 206010052015 cytokine release syndrome Diseases 0.000 claims description 33
- 210000003169 central nervous system Anatomy 0.000 claims description 30
- 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims description 29
- 239000003540 gamma secretase inhibitor Substances 0.000 claims description 29
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 claims description 28
- -1 PF-5212362 Chemical compound 0.000 claims description 25
- 208000015181 infectious disease Diseases 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 238000001959 radiotherapy Methods 0.000 claims description 23
- 238000011269 treatment regimen Methods 0.000 claims description 23
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 22
- 208000035475 disorder Diseases 0.000 claims description 22
- 150000003431 steroids Chemical class 0.000 claims description 20
- 238000001356 surgical procedure Methods 0.000 claims description 20
- 230000001965 increasing effect Effects 0.000 claims description 19
- 230000036210 malignancy Effects 0.000 claims description 19
- 108010003415 Aspartate Aminotransferases Proteins 0.000 claims description 18
- 102000004625 Aspartate Aminotransferases Human genes 0.000 claims description 18
- 239000012270 PD-1 inhibitor Substances 0.000 claims description 18
- 239000012668 PD-1-inhibitor Substances 0.000 claims description 18
- 239000002246 antineoplastic agent Substances 0.000 claims description 18
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 18
- 229940121655 pd-1 inhibitor Drugs 0.000 claims description 18
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 18
- 108090000623 proteins and genes Proteins 0.000 claims description 18
- 150000003384 small molecules Chemical class 0.000 claims description 18
- 231100000433 cytotoxic Toxicity 0.000 claims description 17
- 230000001472 cytotoxic effect Effects 0.000 claims description 17
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 claims description 16
- 108010082126 Alanine transaminase Proteins 0.000 claims description 16
- 229930006000 Sucrose Natural products 0.000 claims description 16
- 102100038968 WAP four-disulfide core domain protein 1 Human genes 0.000 claims description 16
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 16
- 229940034982 antineoplastic agent Drugs 0.000 claims description 16
- 239000003638 chemical reducing agent Substances 0.000 claims description 16
- 235000018102 proteins Nutrition 0.000 claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- 210000002966 serum Anatomy 0.000 claims description 16
- 239000005720 sucrose Substances 0.000 claims description 16
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 15
- 239000003112 inhibitor Substances 0.000 claims description 15
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 14
- 239000003207 proteasome inhibitor Substances 0.000 claims description 14
- 229940088597 hormone Drugs 0.000 claims description 13
- 239000005556 hormone Substances 0.000 claims description 13
- 238000001990 intravenous administration Methods 0.000 claims description 13
- 229960003989 tocilizumab Drugs 0.000 claims description 13
- 241000711549 Hepacivirus C Species 0.000 claims description 12
- 210000001185 bone marrow Anatomy 0.000 claims description 12
- 238000002650 immunosuppressive therapy Methods 0.000 claims description 12
- 230000000977 initiatory effect Effects 0.000 claims description 12
- 230000001988 toxicity Effects 0.000 claims description 12
- 231100000419 toxicity Toxicity 0.000 claims description 12
- PKXWXXPNHIWQHW-RCBQFDQVSA-N (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide Chemical compound C1CN(C)C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](O)C(C)C)C2=CC=CC=C21 PKXWXXPNHIWQHW-RCBQFDQVSA-N 0.000 claims description 11
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 11
- 206010020751 Hypersensitivity Diseases 0.000 claims description 11
- 101710085938 Matrix protein Proteins 0.000 claims description 11
- 101710127721 Membrane protein Proteins 0.000 claims description 11
- 229940109239 creatinine Drugs 0.000 claims description 11
- 239000003102 growth factor Substances 0.000 claims description 11
- 230000009885 systemic effect Effects 0.000 claims description 11
- 229960005486 vaccine Drugs 0.000 claims description 11
- XCGJIFAKUZNNOR-UHFFFAOYSA-N 3-[4-(4-chlorophenyl)sulfonyl-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid Chemical compound C1CC(CCC(=O)O)CCC1(S(=O)(=O)C=1C=CC(Cl)=CC=1)C1=CC(F)=CC=C1F XCGJIFAKUZNNOR-UHFFFAOYSA-N 0.000 claims description 10
- XEAOPVUAMONVLA-QGZVFWFLSA-N Avagacestat Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)N([C@H](CCC(F)(F)F)C(=O)N)CC(C(=C1)F)=CC=C1C=1N=CON=1 XEAOPVUAMONVLA-QGZVFWFLSA-N 0.000 claims description 10
- 229940125563 LAG3 inhibitor Drugs 0.000 claims description 10
- 206010027476 Metastases Diseases 0.000 claims description 10
- 102100032965 Myomesin-2 Human genes 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 230000003211 malignant effect Effects 0.000 claims description 10
- 230000001954 sterilising effect Effects 0.000 claims description 10
- 238000004659 sterilization and disinfection Methods 0.000 claims description 10
- VFCRKLWBYMDAED-REWPJTCUSA-N (2s)-2-[[(2s)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]amino]-n-[1-[1-(2,2-dimethylpropylamino)-2-methylpropan-2-yl]imidazol-4-yl]pentanamide Chemical compound O=C([C@@H](N[C@@H]1CC2=C(F)C=C(F)C=C2CC1)CCC)NC1=CN(C(C)(C)CNCC(C)(C)C)C=N1 VFCRKLWBYMDAED-REWPJTCUSA-N 0.000 claims description 9
- YCBAQKQAINQRFW-UGSOOPFHSA-N 4,4,4-trifluoro-n-[(2s)-1-[[(7s)-5-(2-hydroxyethyl)-6-oxo-7h-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-oxopropan-2-yl]butanamide Chemical compound OCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)CCC(F)(F)F)C)C2=CC=CC=C2C2=CC=CN=C21 YCBAQKQAINQRFW-UGSOOPFHSA-N 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 9
- DWJXYEABWRJFSP-XOBRGWDASA-N DAPT Chemical compound N([C@@H](C)C(=O)N[C@H](C(=O)OC(C)(C)C)C=1C=CC=CC=1)C(=O)CC1=CC(F)=CC(F)=C1 DWJXYEABWRJFSP-XOBRGWDASA-N 0.000 claims description 9
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 9
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 9
- 241000700721 Hepatitis B virus Species 0.000 claims description 9
- ULSSJYNJIZWPSB-CVRXJBIPSA-N LY-411575 Chemical compound C1([C@H](O)C(=O)N[C@@H](C)C(=O)N[C@@H]2C(N(C)C3=CC=CC=C3C3=CC=CC=C32)=O)=CC(F)=CC(F)=C1 ULSSJYNJIZWPSB-CVRXJBIPSA-N 0.000 claims description 9
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 9
- 239000003246 corticosteroid Substances 0.000 claims description 9
- 229960001334 corticosteroids Drugs 0.000 claims description 9
- 208000019622 heart disease Diseases 0.000 claims description 9
- 201000005787 hematologic cancer Diseases 0.000 claims description 9
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 9
- KTCJYACFOQWRDO-GOSISDBHSA-N n-[(4-bromophenyl)methyl]-4-chloro-n-[(3r)-2-oxoazepan-3-yl]benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N([C@H]1C(NCCCC1)=O)CC1=CC=C(Br)C=C1 KTCJYACFOQWRDO-GOSISDBHSA-N 0.000 claims description 9
- IZAOBRWCUGOKNH-OAHLLOKOSA-N 4-[2-[(1R)-1-(N-(4-chlorophenyl)sulfonyl-2,5-difluoroanilino)ethyl]-5-fluorophenyl]butanoic acid Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)N([C@H](C)C=1C(=CC(F)=CC=1)CCCC(O)=O)C1=CC(F)=CC=C1F IZAOBRWCUGOKNH-OAHLLOKOSA-N 0.000 claims description 8
- 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 claims description 8
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 8
- 238000011977 dual antiplatelet therapy Methods 0.000 claims description 8
- 230000003054 hormonal effect Effects 0.000 claims description 8
- 229960004584 methylprednisolone Drugs 0.000 claims description 8
- 229950007213 spartalizumab Drugs 0.000 claims description 8
- AYOUDDAETNMCBW-GSHUGGBRSA-N (2S,3R)-N'-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)butanediamide Chemical compound O=C([C@@H](NC(=O)[C@H](CCC(F)(F)F)[C@H](CCC(F)(F)F)C(N)=O)N=1)N(C)C2=CC=CC=C2C=1C1=CC=CC=C1 AYOUDDAETNMCBW-GSHUGGBRSA-N 0.000 claims description 7
- 206010061728 Bone lesion Diseases 0.000 claims description 7
- 229960001467 bortezomib Drugs 0.000 claims description 7
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 7
- 229960002438 carfilzomib Drugs 0.000 claims description 7
- 108010021331 carfilzomib Proteins 0.000 claims description 7
- BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 claims description 7
- 229960002204 daratumumab Drugs 0.000 claims description 7
- 229960004942 lenalidomide Drugs 0.000 claims description 7
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims description 7
- 229960005489 paracetamol Drugs 0.000 claims description 7
- 229960000688 pomalidomide Drugs 0.000 claims description 7
- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 claims description 7
- 238000012216 screening Methods 0.000 claims description 7
- 229940126634 CD38 inhibitor Drugs 0.000 claims description 6
- 208000035473 Communicable disease Diseases 0.000 claims description 6
- 206010061818 Disease progression Diseases 0.000 claims description 6
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 6
- 102000036693 Thrombopoietin Human genes 0.000 claims description 6
- 108010041111 Thrombopoietin Proteins 0.000 claims description 6
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 6
- 230000005750 disease progression Effects 0.000 claims description 6
- 239000003862 glucocorticoid Substances 0.000 claims description 6
- 230000004217 heart function Effects 0.000 claims description 6
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 229960004618 prednisone Drugs 0.000 claims description 6
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 6
- 208000020446 Cardiac disease Diseases 0.000 claims description 5
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 5
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 5
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims description 5
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims description 5
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 5
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 5
- 206010053869 POEMS syndrome Diseases 0.000 claims description 5
- 208000002774 Paraproteinemias Diseases 0.000 claims description 5
- 206010036105 Polyneuropathy Diseases 0.000 claims description 5
- 230000000735 allogeneic effect Effects 0.000 claims description 5
- 239000002269 analeptic agent Substances 0.000 claims description 5
- 230000002281 colonystimulating effect Effects 0.000 claims description 5
- 208000030172 endocrine system disease Diseases 0.000 claims description 5
- 230000000925 erythroid effect Effects 0.000 claims description 5
- 230000003394 haemopoietic effect Effects 0.000 claims description 5
- 229940121569 ieramilimab Drugs 0.000 claims description 5
- 239000002955 immunomodulating agent Substances 0.000 claims description 5
- 229940121354 immunomodulator Drugs 0.000 claims description 5
- 230000002584 immunomodulator Effects 0.000 claims description 5
- 230000001506 immunosuppresive effect Effects 0.000 claims description 5
- 230000001771 impaired effect Effects 0.000 claims description 5
- 230000002101 lytic effect Effects 0.000 claims description 5
- 230000007823 neuropathy Effects 0.000 claims description 5
- 201000001119 neuropathy Diseases 0.000 claims description 5
- 210000000440 neutrophil Anatomy 0.000 claims description 5
- 229960003301 nivolumab Drugs 0.000 claims description 5
- 230000000474 nursing effect Effects 0.000 claims description 5
- 229960002621 pembrolizumab Drugs 0.000 claims description 5
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
- 229950010773 pidilizumab Drugs 0.000 claims description 5
- 208000031223 plasma cell leukemia Diseases 0.000 claims description 5
- 208000010626 plasma cell neoplasm Diseases 0.000 claims description 5
- 230000007824 polyneuropathy Effects 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 208000020016 psychiatric disease Diseases 0.000 claims description 5
- 238000009121 systemic therapy Methods 0.000 claims description 5
- 231100000331 toxic Toxicity 0.000 claims description 5
- 230000002588 toxic effect Effects 0.000 claims description 5
- 210000002700 urine Anatomy 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 208000007814 Unstable Angina Diseases 0.000 claims description 4
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 4
- 239000000611 antibody drug conjugate Substances 0.000 claims description 4
- 206010003119 arrhythmia Diseases 0.000 claims description 4
- 230000006793 arrhythmia Effects 0.000 claims description 4
- 208000015700 familial long QT syndrome Diseases 0.000 claims description 4
- 102000046935 human TNFRSF17 Human genes 0.000 claims description 4
- 229940124622 immune-modulator drug Drugs 0.000 claims description 4
- 206010022000 influenza Diseases 0.000 claims description 4
- 229940044953 vaginal ring Drugs 0.000 claims description 4
- 239000006213 vaginal ring Substances 0.000 claims description 4
- 230000003442 weekly effect Effects 0.000 claims description 4
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- 229940125715 antihistaminic agent Drugs 0.000 claims description 3
- 229960001838 canakinumab Drugs 0.000 claims description 3
- VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 claims 4
- 238000009472 formulation Methods 0.000 abstract description 11
- 230000006806 disease prevention Effects 0.000 abstract 1
- 239000000427 antigen Substances 0.000 description 79
- 102000036639 antigens Human genes 0.000 description 79
- 108091007433 antigens Proteins 0.000 description 79
- 150000003839 salts Chemical class 0.000 description 31
- 235000001014 amino acid Nutrition 0.000 description 24
- 210000003719 b-lymphocyte Anatomy 0.000 description 24
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 23
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 23
- 108060003951 Immunoglobulin Proteins 0.000 description 22
- 102000018358 immunoglobulin Human genes 0.000 description 22
- 229940024606 amino acid Drugs 0.000 description 21
- 229940121773 Secretase inhibitor Drugs 0.000 description 19
- 125000000539 amino acid group Chemical group 0.000 description 19
- 238000003556 assay Methods 0.000 description 19
- 201000000050 myeloid neoplasm Diseases 0.000 description 19
- 208000024891 symptom Diseases 0.000 description 19
- 239000012636 effector Substances 0.000 description 18
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 17
- 239000012634 fragment Substances 0.000 description 17
- 125000003275 alpha amino acid group Chemical group 0.000 description 16
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 16
- 230000006870 function Effects 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 15
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 15
- 108091008874 T cell receptors Proteins 0.000 description 14
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 14
- 102000039446 nucleic acids Human genes 0.000 description 14
- 230000001404 mediated effect Effects 0.000 description 13
- 239000013598 vector Substances 0.000 description 13
- 231100000682 maximum tolerated dose Toxicity 0.000 description 12
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 11
- 238000012042 bayesian logistic regression model Methods 0.000 description 11
- 108010087819 Fc receptors Proteins 0.000 description 10
- 102000009109 Fc receptors Human genes 0.000 description 10
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 10
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 230000000295 complement effect Effects 0.000 description 9
- 230000007717 exclusion Effects 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 108060001084 Luciferase Proteins 0.000 description 7
- 239000005089 Luciferase Substances 0.000 description 7
- 230000009089 cytolysis Effects 0.000 description 7
- 238000007726 management method Methods 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 210000004180 plasmocyte Anatomy 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 241000282567 Macaca fascicularis Species 0.000 description 6
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 230000000996 additive effect Effects 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 230000000069 prophylactic effect Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 5
- 229940124572 antihypotensive agent Drugs 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 239000000833 heterodimer Substances 0.000 description 5
- 208000003532 hypothyroidism Diseases 0.000 description 5
- 230000002989 hypothyroidism Effects 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000009097 single-agent therapy Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000005526 vasoconstrictor agent Substances 0.000 description 5
- 229940124648 γ-Secretase Modulator Drugs 0.000 description 5
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 4
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 231100001273 GLP toxicology study Toxicity 0.000 description 4
- 208000017604 Hodgkin disease Diseases 0.000 description 4
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 4
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 4
- 201000004681 Psoriasis Diseases 0.000 description 4
- 230000006052 T cell proliferation Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229960002748 norepinephrine Drugs 0.000 description 4
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 4
- 238000009806 oophorectomy Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 230000009257 reactivity Effects 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 208000011691 Burkitt lymphomas Diseases 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 208000001953 Hypotension Diseases 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 108010065323 Tumor Necrosis Factor Ligand Superfamily Member 13 Proteins 0.000 description 3
- 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 description 3
- 108010004977 Vasopressins Proteins 0.000 description 3
- 102000002852 Vasopressins Human genes 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000003044 adaptive effect Effects 0.000 description 3
- 238000011374 additional therapy Methods 0.000 description 3
- 230000003092 anti-cytokine Effects 0.000 description 3
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 238000002565 electrocardiography Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000005734 heterodimerization reaction Methods 0.000 description 3
- 239000000710 homodimer Substances 0.000 description 3
- 230000036543 hypotension Effects 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 210000001806 memory b lymphocyte Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000003285 pharmacodynamic effect Effects 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- PSXOKXJMVRSARX-SCSAIBSYSA-N 5-chloro-n-[(2s)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl]thiophene-2-sulfonamide Chemical compound FC(F)(F)C(C(F)(F)F)[C@@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 PSXOKXJMVRSARX-SCSAIBSYSA-N 0.000 description 2
- 206010002412 Angiocentric lymphomas Diseases 0.000 description 2
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 208000009458 Carcinoma in Situ Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 206010051792 Infusion related reaction Diseases 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 2
- 201000003791 MALT lymphoma Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 2
- 102000015094 Paraproteins Human genes 0.000 description 2
- 108010064255 Paraproteins Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 208000007452 Plasmacytoma Diseases 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 2
- 206010054094 Tumour necrosis Diseases 0.000 description 2
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 2
- 206010047642 Vitiligo Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 229960000548 alemtuzumab Drugs 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 230000001494 anti-thymocyte effect Effects 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 229940125683 antiemetic agent Drugs 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 229940125716 antipyretic agent Drugs 0.000 description 2
- 201000007201 aphasia Diseases 0.000 description 2
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000000270 basal cell Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 230000001447 compensatory effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229960005139 epinephrine Drugs 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 201000003444 follicular lymphoma Diseases 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000004837 gut-associated lymphoid tissue Anatomy 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 238000009802 hysterectomy Methods 0.000 description 2
- 201000004933 in situ carcinoma Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 238000009092 lines of therapy Methods 0.000 description 2
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 2
- 208000021937 marginal zone lymphoma Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000009149 molecular binding Effects 0.000 description 2
- 230000004001 molecular interaction Effects 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 108010068617 neonatal Fc receptor Proteins 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 238000004091 panning Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 210000003720 plasmablast Anatomy 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 229950001900 semagacestat Drugs 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 208000010721 smoldering plasma cell myeloma Diseases 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000934 spermatocidal agent Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000003319 supportive effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002636 symptomatic treatment Methods 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000009804 total hysterectomy Methods 0.000 description 2
- 231100000816 toxic dose Toxicity 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000009810 tubal ligation Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000006216 vaginal suppository Substances 0.000 description 2
- 229940120293 vaginal suppository Drugs 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 229960003726 vasopressin Drugs 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- QSHGISMANBKLQL-OWJWWREXSA-N (2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-[(7s)-5-methyl-6-oxo-7h-benzo[d][1]benzazepin-7-yl]propanamide Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C2=CC=CC=C21)=O)C(=O)CC1=CC(F)=CC(F)=C1 QSHGISMANBKLQL-OWJWWREXSA-N 0.000 description 1
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- PSXOKXJMVRSARX-BYPYZUCNSA-N 5-chloro-n-[(2r)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl]thiophene-2-sulfonamide Chemical compound FC(F)(F)C(C(F)(F)F)[C@H](CO)NS(=O)(=O)C1=CC=C(Cl)S1 PSXOKXJMVRSARX-BYPYZUCNSA-N 0.000 description 1
- LCGTWRLJTMHIQZ-UHFFFAOYSA-N 5H-dibenzo[b,f]azepine Chemical compound C1=CC2=CC=CC=C2NC2=CC=CC=C21 LCGTWRLJTMHIQZ-UHFFFAOYSA-N 0.000 description 1
- AMDGKLWVCUXONP-UHFFFAOYSA-N 7-amino-4-chloro-3-methoxy-2-benzopyran-1-one Chemical compound NC1=CC=C2C(Cl)=C(OC)OC(=O)C2=C1 AMDGKLWVCUXONP-UHFFFAOYSA-N 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 206010001935 American trypanosomiasis Diseases 0.000 description 1
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 1
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 206010008072 Cerebellar syndrome Diseases 0.000 description 1
- 208000024699 Chagas disease Diseases 0.000 description 1
- 206010008531 Chills Diseases 0.000 description 1
- 208000032862 Clinical Deterioration Diseases 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 239000003154 D dimer Substances 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 102000008857 Ferritin Human genes 0.000 description 1
- 108050000784 Ferritin Proteins 0.000 description 1
- 238000008416 Ferritin Methods 0.000 description 1
- 102000002090 Fibronectin type III Human genes 0.000 description 1
- 108050009401 Fibronectin type III Proteins 0.000 description 1
- 206010016803 Fluid overload Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010051125 Hypofibrinogenaemia Diseases 0.000 description 1
- 206010053574 Immunoblastic lymphoma Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 208000022120 Jeavons syndrome Diseases 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000282561 Macaca nemestrina Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010048294 Mental status changes Diseases 0.000 description 1
- 208000010190 Monoclonal Gammopathy of Undetermined Significance Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100288142 Mus musculus Klkb1 gene Proteins 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 102000005717 Myeloma Proteins Human genes 0.000 description 1
- 108010045503 Myeloma Proteins Proteins 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 101000579647 Penaeus vannamei Penaeidin-2a Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000015499 Presenilins Human genes 0.000 description 1
- 108010050254 Presenilins Proteins 0.000 description 1
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229940044665 STING agonist Drugs 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 208000004346 Smoldering Multiple Myeloma Diseases 0.000 description 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 229940124675 anti-cancer drug Drugs 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000001062 anti-nausea Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940127079 antineoplastic immunimodulatory agent Drugs 0.000 description 1
- 101150089041 aph-1 gene Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 229950008567 avagacestat Drugs 0.000 description 1
- 229950008971 begacestat Drugs 0.000 description 1
- OWCDMRFUFMERMZ-UHFFFAOYSA-N benzenesulfonamide;hydrochloride Chemical compound Cl.NS(=O)(=O)C1=CC=CC=C1 OWCDMRFUFMERMZ-UHFFFAOYSA-N 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- WJQLUFQGNVGLKR-SZMVWBNQSA-N benzyl n-[(2s,3s)-3-methyl-1-[[(2s)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)OCC1=CC=CC=C1 WJQLUFQGNVGLKR-SZMVWBNQSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 208000027119 bilirubin metabolic disease Diseases 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- NKHUILHBYOOZDF-NCOIWELASA-N chembl196215 Chemical compound N1S(=O)(=O)N(CC(F)(F)F)C[C@]21[C@@H]1CC[C@H]2CC2=CC=C(\C=C\CN3CCC(CC3)C(F)(F)F)C=C2C1 NKHUILHBYOOZDF-NCOIWELASA-N 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011278 co-treatment Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 229950009663 crenigacestat Drugs 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 108010052295 fibrin fragment D Proteins 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 208000025750 heavy chain disease Diseases 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 208000011316 hemodynamic instability Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 208000036796 hyperbilirubinemia Diseases 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000018875 hypoxemia Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000000495 immunoinflammatory effect Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000002809 long lived plasma cell Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 208000006116 lymphomatoid granulomatosis Diseases 0.000 description 1
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- WRIRWRKPLXCTFD-UHFFFAOYSA-N malonamide Chemical compound NC(=O)CC(N)=O WRIRWRKPLXCTFD-UHFFFAOYSA-N 0.000 description 1
- 210000003826 marginal zone b cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005399 mechanical ventilation Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 208000014981 mild hypotension Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 102000046701 nicastrin Human genes 0.000 description 1
- 108700022821 nicastrin Proteins 0.000 description 1
- 229950001637 nirogacestat Drugs 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 230000014207 opsonization Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 208000017805 post-transplant lymphoproliferative disease Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 201000006037 primary mediastinal B-cell lymphoma Diseases 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000035485 pulse pressure Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 201000008158 rapidly progressive glomerulonephritis Diseases 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011867 re-evaluation Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 210000002707 regulatory b cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 229960003323 siltuximab Drugs 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 201000009295 smoldering myeloma Diseases 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 208000008203 tachypnea Diseases 0.000 description 1
- 206010043089 tachypnoea Diseases 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 229940044616 toll-like receptor 7 agonist Drugs 0.000 description 1
- 231100000155 toxicity by organ Toxicity 0.000 description 1
- 230000007675 toxicity by organ Effects 0.000 description 1
- 231100001072 toxicokinetic profile Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000001296 transplacental effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/417—Imidazole-alkylamines, e.g. histamine, phentolamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962865381P | 2019-06-24 | 2019-06-24 | |
US62/865,381 | 2019-06-24 | ||
US201962940589P | 2019-11-26 | 2019-11-26 | |
US62/940,589 | 2019-11-26 | ||
US202062967401P | 2020-01-29 | 2020-01-29 | |
US62/967,401 | 2020-01-29 | ||
US202063034106P | 2020-06-03 | 2020-06-03 | |
US63/034,106 | 2020-06-03 | ||
PCT/IB2020/055872 WO2020261093A1 (en) | 2019-06-24 | 2020-06-22 | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen |
Publications (1)
Publication Number | Publication Date |
---|---|
CA3144324A1 true CA3144324A1 (en) | 2020-12-30 |
Family
ID=71738213
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA3144324A Pending CA3144324A1 (en) | 2019-06-24 | 2020-06-22 | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen |
Country Status (10)
Country | Link |
---|---|
US (1) | US20220332821A1 (zh) |
EP (1) | EP3986569A1 (zh) |
JP (1) | JP2022538237A (zh) |
KR (1) | KR20220024729A (zh) |
CN (1) | CN114286828A (zh) |
AU (1) | AU2020307471A1 (zh) |
CA (1) | CA3144324A1 (zh) |
IL (1) | IL289187A (zh) |
TW (1) | TW202115114A (zh) |
WO (1) | WO2020261093A1 (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL274151B (en) | 2015-05-21 | 2022-07-01 | Harpoon Therapeutics Inc | Trispecific binding proteins and methods of use |
US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
US20200179511A1 (en) * | 2017-04-28 | 2020-06-11 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
CR20200195A (es) | 2017-10-13 | 2020-08-14 | Harpoon Therapeutics Inc | Proteínas de unión a antigenos de maduraciòn de celulas b |
AU2019346466A1 (en) | 2018-09-25 | 2021-05-20 | Harpoon Therapeutics, Inc. | DLL3 binding proteins and methods of use |
WO2021228783A1 (en) | 2020-05-11 | 2021-11-18 | Janssen Pharmaceutica Nv | Methods for treating multiple myeloma |
WO2023284806A1 (zh) * | 2021-07-14 | 2023-01-19 | 江苏恒瑞医药股份有限公司 | 特异性结合cd38、bcma和cd3的抗原结合分子及其医药用途 |
CN113908395B (zh) * | 2021-10-13 | 2024-05-17 | 科悦医疗(苏州)有限公司 | 一种促醒仪 |
IL312503A (en) * | 2021-11-03 | 2024-07-01 | Janssen Biotech Inc | Methods for treating cancer and improving the efficacy of BCMAXCD3 bispecific antibodies |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US5942400A (en) | 1995-06-07 | 1999-08-24 | Elan Pharmaceuticals, Inc. | Assays for detecting β-secretase |
DK0985039T3 (da) | 1997-06-12 | 2008-06-09 | Novartis Int Pharm Ltd | Kunstige antistof-polypeptider |
US7468365B2 (en) | 2000-11-17 | 2008-12-23 | Eli Lilly And Company | Lactam compound |
GB0120347D0 (en) | 2001-08-21 | 2001-10-17 | Merck Sharp & Dohme | Therapeutic agents |
ATE428698T1 (de) | 2003-09-09 | 2009-05-15 | Hoffmann La Roche | Die aktivität von gamma-secretase blockierende malonamidderivate |
US7208488B2 (en) | 2003-10-29 | 2007-04-24 | Elan Pharmaceuticals, Inc. | N-substituted benzene sulfonamides |
US20070161700A1 (en) | 2004-12-28 | 2007-07-12 | Kowa Company, Ltd. | Inhibitor for the formation of y-secretase complex |
DE602005007717D1 (de) | 2004-03-23 | 2008-08-07 | Pfizer Prod Inc | Imidazolverbindungen zur behandlung von neurodegenerativen erkrankungen |
KR20080093126A (ko) | 2006-02-17 | 2008-10-20 | 와이어쓰 | 술폰아미드 치환된 알코올 및 이의 중간체의 제조 방법 |
JP5311303B2 (ja) | 2006-04-25 | 2013-10-09 | 国立大学法人 東京大学 | アルツハイマー病および癌の治療薬 |
CA2695864A1 (en) | 2007-08-07 | 2009-02-12 | Schering Corporation | Gamma secretase modulators |
BRPI0815135A2 (pt) | 2007-08-14 | 2015-02-03 | Lilly Co Eli | Derivados de azepina como inibidores de gama secretase. |
US8084477B2 (en) | 2007-10-31 | 2011-12-27 | Bristol-Myers Squibb Company | Alpha-(N-sulfonamido)acetamide compound as an inhibitor of beta amyloid peptide production |
TWI530489B (zh) | 2011-03-22 | 2016-04-21 | 必治妥美雅史谷比公司 | 雙(氟烷基)-1,4-苯二氮呯酮化合物 |
WO2013066740A1 (en) | 2011-10-31 | 2013-05-10 | Merck Sharp & Dohme Corp. | Gamma secretase modulators |
TWI679212B (zh) * | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對bcma之e3以及cd3的結合分子 |
WO2014085211A2 (en) | 2012-11-29 | 2014-06-05 | Merck Sharp & Dohme Corp. | Spirocyclic sulfones as gamma secretase inhibitors |
CN108064244B (zh) * | 2014-11-14 | 2021-09-17 | 诺华股份有限公司 | 抗体药物缀合物 |
AU2015353416C1 (en) * | 2014-11-26 | 2022-01-27 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and CD38 |
IL290488B2 (en) | 2015-04-13 | 2024-07-01 | Pfizer | Therapeutic antibodies and their uses |
CN108025001A (zh) | 2015-07-24 | 2018-05-11 | 安可初克公司 | 用于治疗免疫系统功能障碍的γ分泌酶调节剂 |
EP3411068A4 (en) * | 2016-02-02 | 2020-01-29 | Kadmon Corporation, LLC | BISPECIFIC BINDING PROTEINS FOR PD-L1 AND KDR |
BR112019008426A2 (pt) * | 2016-11-02 | 2019-09-03 | Engmab Sarl | anticorpo biespecífico contra bcma e cd3 e um fármaco imunológico para uso combinado no tratamento de mieloma múltiplo |
US20200179511A1 (en) * | 2017-04-28 | 2020-06-11 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
KR20210016390A (ko) * | 2018-06-01 | 2021-02-15 | 노파르티스 아게 | Bcma에 대한 결합 분자 및 이의 용도 |
-
2020
- 2020-06-22 CA CA3144324A patent/CA3144324A1/en active Pending
- 2020-06-22 US US17/620,987 patent/US20220332821A1/en active Pending
- 2020-06-22 JP JP2021576635A patent/JP2022538237A/ja active Pending
- 2020-06-22 TW TW109121083A patent/TW202115114A/zh unknown
- 2020-06-22 CN CN202080059452.0A patent/CN114286828A/zh active Pending
- 2020-06-22 KR KR1020227001880A patent/KR20220024729A/ko unknown
- 2020-06-22 EP EP20743802.9A patent/EP3986569A1/en active Pending
- 2020-06-22 WO PCT/IB2020/055872 patent/WO2020261093A1/en unknown
- 2020-06-22 AU AU2020307471A patent/AU2020307471A1/en not_active Abandoned
-
2021
- 2021-12-20 IL IL289187A patent/IL289187A/en unknown
Also Published As
Publication number | Publication date |
---|---|
AU2020307471A1 (en) | 2022-01-27 |
WO2020261093A1 (en) | 2020-12-30 |
IL289187A (en) | 2022-02-01 |
US20220332821A1 (en) | 2022-10-20 |
EP3986569A1 (en) | 2022-04-27 |
TW202115114A (zh) | 2021-04-16 |
JP2022538237A (ja) | 2022-09-01 |
CN114286828A (zh) | 2022-04-05 |
KR20220024729A (ko) | 2022-03-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20220332821A1 (en) | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen | |
JP7174009B2 (ja) | Pd-1に対するヒト抗体 | |
JP6865324B2 (ja) | 抗cd3抗体、cd3及びcd20に結合する二重特異性抗原結合分子、並びにそれらの使用 | |
JP6563472B2 (ja) | 抗ErbB3抗体およびその使用 | |
JP6872537B2 (ja) | 抗lag3抗体およびその使用 | |
CN112384534A (zh) | 用于增强nk细胞对靶细胞的杀死的组合物和方法 | |
JP6367233B2 (ja) | 抗pdgfr−ベータ抗体及びそれらの使用 | |
JP7244938B2 (ja) | 多価及び多重特異性dr5結合融合タンパク質 | |
IL263611A (en) | Antibodies specific to PD-L1 and methods of using them | |
TW202128759A (zh) | 結合nkg2d、cd及flt3之蛋白質 | |
US20240109963A1 (en) | Multispecific antibodies and uses thereof | |
JP2021503911A (ja) | 抗ox40抗体及びその用途 | |
WO2022098771A1 (en) | Multispecific antibodies and uses thereof | |
WO2022256563A1 (en) | Anti-ccr8 antibodies and uses thereof | |
CN114929343A (zh) | 用双特异性抗BCMA x抗CD3抗体治疗多发性骨髓瘤的方法 | |
US20240270861A1 (en) | Proteins binding nkg2d, cd16 and baff-r | |
US20240124607A1 (en) | Proteins binding nkg2d, cd16, and ceacam5 | |
JP2021501583A (ja) | 抗体および使用方法 | |
JP7566923B2 (ja) | 抗gitr抗体およびその使用 | |
RU2819624C2 (ru) | Композиции анти-cd112r антител и сопутствующие способы | |
WO2022097090A1 (en) | Dosing regimen for combination therapies with multispecific antibodies targeting b-cell maturation antigen and gamma secretase inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request |
Effective date: 20220926 |
|
EEER | Examination request |
Effective date: 20220926 |
|
EEER | Examination request |
Effective date: 20220926 |